Personalized tumor vaccines based on carrier-free double-adjuvant nanoparticles and tumor-associated antigens for enhancing immune responses

Immune adjuvants are extremely important in tumor vaccines, which can amplify antigen-specific immune responses and enhance anti-tumor efficacy. Nevertheless, well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines. In this study, we designed and formulated carrier-free double-adjuvant nanoparticles (FPC-NPs) by self-assembling of fluoroalkane-grafted polyethylenimide (PEI) (Toll-like receptor 4 (TLR4) agonist) and cytosine-phosphate-guanine (CpG) (TLR9 agonist), and then obtained personalized tumor vaccines (FPC-NPs@TAAs) by electrostatic adsorption of tumor-associated antigens (TAAs) on the surface of FPC-NPs. The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants, deliver antigens and adjuvants to the same antigen-presenting cell, which can effectively activate dendritic cells, encourage cross-presentation of antigens, and reduce the proportion of M2-type macrophages. Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles , showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy . Self-assembled carrier-free double-adjuvant nanoparticles prepared by electrostatic adsorption of F-PEI and CpG can capture tumor-associated antigens to form personalized tumor vaccines and enhance immune responses through activating both TLR4 and TLR9 pathways.